Thyroid Cancer Metastasis Genes

Thyroid cancer is the most common malignancy in the endocrine system and its incidence have been rising in the past few decades with vast majority of this increase being ascribed to papillary thyroid carcinoma (PTC).The rise in incidence seems to be due to over-diagnosis, but an actual increase in incidence and mortality cannot be ruled out. Metastasis is the leading cause of cancer mortality including thyroid cancer. The metastatic cascade represents a multi-step process which includes local tumor cell invasion, entry into the vasculature followed by the exit of cancer cells from the circulation and colonization at the distal sites. Distant metastasis occur in about 10% of PTC and up to 25% follicular thyroid carcinoma (FTC) patients. The lungs (~80%) and bones (~25%) are the most common sites for distant metastasis with overall survival of about 10 months in patients with metastases to the lung and 23 months to the bone.

Activation of metastatic reprogramming and survival of circulating tumor cells in the blood circulation with eventual colonization at distant organs are critical steps for thyroid cancer metastasis, which are influenced by both tumor intrinsic (genetic mutations and epigenetic modifications) and extrinsic factors (tumor microenvironment or TME). However, detailed mechanisms contributing to thyroid cancer metastasis are still lacking. Understanding the underlying mechanisms would enable targeted intervention. The present study investigates the mechanisms of how circulating tumor cells survive in the blood circulation and colonize at lung by using cell lines derived from genetically engineered mouse models of PTC, FTC, PDTC, and ATC, representing the whole spectrum of thyroid carcinogenesis. We intend to uncover key genes and pathways involved in the thyroid cancer metastasis as well as biomarkers for prognosis prediction.